Dosimetric evaluation of copper-64 in copper-67-2IT-BAT-Lym-1 for radioimmunotherapy

Sui Shen, Gerald L Denardo, Sally J. DeNardo, Qansy Salako, Geoffrey Morris, Danny Banks, Aina Yuan, Diane A. DeNardo

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Copper-67 (67Cu) is an attractive radionuclide for radioimmunotherapy because of its favorable physical and biologic characteristics. Current supplies of 67Cu, however, contain as much as 60% of 64Cu at the time of delivery. Scatter photons from 64Cu enter the 67Cu energy window, affecting image resolution and counting accuracy. The radiation dose to tissue is also altered. Methods: A line source and a small vial source of 67Cu containing varying amounts of 64Cu were used to evaluate the impact of 64Cu on image resolution and activity quantitation, respectively. Identical pharmacokinetics for 67Cu and 64Cu was assumed, and the radiation dosimetry of 64Cu was assessed using quantitative imaging data for 67Cu because the amount of 64Cu could be calculated for any time after 67Cu production. MIRD formalism was used to estimate the therapeutic index, defined as the ratio of radiation dose to tumor divided by the radiation dose to bone marrow. Results: As the amount of 64Cu increased, the full width at tenth maximum of the line spread function increased, although there was no significant change in full width at half maximum. The number of scatter counts from 64Cu increased as the amount of 64Cu or the size of the source region of interest increased. When 64Cu was 25% of the total activity, less than 10% of the total 67Cu photopeak counts detected with a scintillation camera were attributable to 64Cu, although the tumor radiation dose per unit of activity (cGy/GBq) from 67Cu was five times greater than that from 64Cu, the marrow dose (cGy/GBq) from 67Cu was only three times greater than that from 64Cu. Therefore, the therapeutic index was diminished by the presence of 64Cu. When 64Cu radioimpurity was less than 25% of the total activity, there was less than a 10% decrease in the therapeutic index. Conclusion: The shorter physical half-life of 64Cu relative to that of 67Cu and slower uptake and longer retention of antibody by tumor than by marrow result in a lower therapeutic index for 646u. The 25% radioimpurity of 64Cu causes less than 10% deviation in activity quantitation and diminution in the therapeutic index. The change in therapeutic index is predictable over time and can be used to determine the optimal time for radiopharmaceutical administration.

Original languageEnglish (US)
Pages (from-to)146-150
Number of pages5
JournalJournal of Nuclear Medicine
Volume37
Issue number1
StatePublished - Jan 1996
Externally publishedYes

Fingerprint

Radioimmunotherapy
Copper
Radiation
Bone Marrow
Therapeutics
Radiometry
Neoplasm Antibodies
Gamma Cameras
Radiopharmaceuticals
Photons
Radioisotopes
Half-Life
copper-67-2IT-BAT-Lym-1
Neoplasms
Pharmacokinetics

Keywords

  • copper-64
  • copper-67
  • radiation dosimetry
  • radioimmunotherapy

ASJC Scopus subject areas

  • Radiological and Ultrasound Technology

Cite this

Shen, S., Denardo, G. L., DeNardo, S. J., Salako, Q., Morris, G., Banks, D., ... DeNardo, D. A. (1996). Dosimetric evaluation of copper-64 in copper-67-2IT-BAT-Lym-1 for radioimmunotherapy. Journal of Nuclear Medicine, 37(1), 146-150.

Dosimetric evaluation of copper-64 in copper-67-2IT-BAT-Lym-1 for radioimmunotherapy. / Shen, Sui; Denardo, Gerald L; DeNardo, Sally J.; Salako, Qansy; Morris, Geoffrey; Banks, Danny; Yuan, Aina; DeNardo, Diane A.

In: Journal of Nuclear Medicine, Vol. 37, No. 1, 01.1996, p. 146-150.

Research output: Contribution to journalArticle

Shen, S, Denardo, GL, DeNardo, SJ, Salako, Q, Morris, G, Banks, D, Yuan, A & DeNardo, DA 1996, 'Dosimetric evaluation of copper-64 in copper-67-2IT-BAT-Lym-1 for radioimmunotherapy', Journal of Nuclear Medicine, vol. 37, no. 1, pp. 146-150.
Shen S, Denardo GL, DeNardo SJ, Salako Q, Morris G, Banks D et al. Dosimetric evaluation of copper-64 in copper-67-2IT-BAT-Lym-1 for radioimmunotherapy. Journal of Nuclear Medicine. 1996 Jan;37(1):146-150.
Shen, Sui ; Denardo, Gerald L ; DeNardo, Sally J. ; Salako, Qansy ; Morris, Geoffrey ; Banks, Danny ; Yuan, Aina ; DeNardo, Diane A. / Dosimetric evaluation of copper-64 in copper-67-2IT-BAT-Lym-1 for radioimmunotherapy. In: Journal of Nuclear Medicine. 1996 ; Vol. 37, No. 1. pp. 146-150.
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title = "Dosimetric evaluation of copper-64 in copper-67-2IT-BAT-Lym-1 for radioimmunotherapy",
abstract = "Copper-67 (67Cu) is an attractive radionuclide for radioimmunotherapy because of its favorable physical and biologic characteristics. Current supplies of 67Cu, however, contain as much as 60{\%} of 64Cu at the time of delivery. Scatter photons from 64Cu enter the 67Cu energy window, affecting image resolution and counting accuracy. The radiation dose to tissue is also altered. Methods: A line source and a small vial source of 67Cu containing varying amounts of 64Cu were used to evaluate the impact of 64Cu on image resolution and activity quantitation, respectively. Identical pharmacokinetics for 67Cu and 64Cu was assumed, and the radiation dosimetry of 64Cu was assessed using quantitative imaging data for 67Cu because the amount of 64Cu could be calculated for any time after 67Cu production. MIRD formalism was used to estimate the therapeutic index, defined as the ratio of radiation dose to tumor divided by the radiation dose to bone marrow. Results: As the amount of 64Cu increased, the full width at tenth maximum of the line spread function increased, although there was no significant change in full width at half maximum. The number of scatter counts from 64Cu increased as the amount of 64Cu or the size of the source region of interest increased. When 64Cu was 25{\%} of the total activity, less than 10{\%} of the total 67Cu photopeak counts detected with a scintillation camera were attributable to 64Cu, although the tumor radiation dose per unit of activity (cGy/GBq) from 67Cu was five times greater than that from 64Cu, the marrow dose (cGy/GBq) from 67Cu was only three times greater than that from 64Cu. Therefore, the therapeutic index was diminished by the presence of 64Cu. When 64Cu radioimpurity was less than 25{\%} of the total activity, there was less than a 10{\%} decrease in the therapeutic index. Conclusion: The shorter physical half-life of 64Cu relative to that of 67Cu and slower uptake and longer retention of antibody by tumor than by marrow result in a lower therapeutic index for 646u. The 25{\%} radioimpurity of 64Cu causes less than 10{\%} deviation in activity quantitation and diminution in the therapeutic index. The change in therapeutic index is predictable over time and can be used to determine the optimal time for radiopharmaceutical administration.",
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AU - Denardo, Gerald L

AU - DeNardo, Sally J.

AU - Salako, Qansy

AU - Morris, Geoffrey

AU - Banks, Danny

AU - Yuan, Aina

AU - DeNardo, Diane A.

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N2 - Copper-67 (67Cu) is an attractive radionuclide for radioimmunotherapy because of its favorable physical and biologic characteristics. Current supplies of 67Cu, however, contain as much as 60% of 64Cu at the time of delivery. Scatter photons from 64Cu enter the 67Cu energy window, affecting image resolution and counting accuracy. The radiation dose to tissue is also altered. Methods: A line source and a small vial source of 67Cu containing varying amounts of 64Cu were used to evaluate the impact of 64Cu on image resolution and activity quantitation, respectively. Identical pharmacokinetics for 67Cu and 64Cu was assumed, and the radiation dosimetry of 64Cu was assessed using quantitative imaging data for 67Cu because the amount of 64Cu could be calculated for any time after 67Cu production. MIRD formalism was used to estimate the therapeutic index, defined as the ratio of radiation dose to tumor divided by the radiation dose to bone marrow. Results: As the amount of 64Cu increased, the full width at tenth maximum of the line spread function increased, although there was no significant change in full width at half maximum. The number of scatter counts from 64Cu increased as the amount of 64Cu or the size of the source region of interest increased. When 64Cu was 25% of the total activity, less than 10% of the total 67Cu photopeak counts detected with a scintillation camera were attributable to 64Cu, although the tumor radiation dose per unit of activity (cGy/GBq) from 67Cu was five times greater than that from 64Cu, the marrow dose (cGy/GBq) from 67Cu was only three times greater than that from 64Cu. Therefore, the therapeutic index was diminished by the presence of 64Cu. When 64Cu radioimpurity was less than 25% of the total activity, there was less than a 10% decrease in the therapeutic index. Conclusion: The shorter physical half-life of 64Cu relative to that of 67Cu and slower uptake and longer retention of antibody by tumor than by marrow result in a lower therapeutic index for 646u. The 25% radioimpurity of 64Cu causes less than 10% deviation in activity quantitation and diminution in the therapeutic index. The change in therapeutic index is predictable over time and can be used to determine the optimal time for radiopharmaceutical administration.

AB - Copper-67 (67Cu) is an attractive radionuclide for radioimmunotherapy because of its favorable physical and biologic characteristics. Current supplies of 67Cu, however, contain as much as 60% of 64Cu at the time of delivery. Scatter photons from 64Cu enter the 67Cu energy window, affecting image resolution and counting accuracy. The radiation dose to tissue is also altered. Methods: A line source and a small vial source of 67Cu containing varying amounts of 64Cu were used to evaluate the impact of 64Cu on image resolution and activity quantitation, respectively. Identical pharmacokinetics for 67Cu and 64Cu was assumed, and the radiation dosimetry of 64Cu was assessed using quantitative imaging data for 67Cu because the amount of 64Cu could be calculated for any time after 67Cu production. MIRD formalism was used to estimate the therapeutic index, defined as the ratio of radiation dose to tumor divided by the radiation dose to bone marrow. Results: As the amount of 64Cu increased, the full width at tenth maximum of the line spread function increased, although there was no significant change in full width at half maximum. The number of scatter counts from 64Cu increased as the amount of 64Cu or the size of the source region of interest increased. When 64Cu was 25% of the total activity, less than 10% of the total 67Cu photopeak counts detected with a scintillation camera were attributable to 64Cu, although the tumor radiation dose per unit of activity (cGy/GBq) from 67Cu was five times greater than that from 64Cu, the marrow dose (cGy/GBq) from 67Cu was only three times greater than that from 64Cu. Therefore, the therapeutic index was diminished by the presence of 64Cu. When 64Cu radioimpurity was less than 25% of the total activity, there was less than a 10% decrease in the therapeutic index. Conclusion: The shorter physical half-life of 64Cu relative to that of 67Cu and slower uptake and longer retention of antibody by tumor than by marrow result in a lower therapeutic index for 646u. The 25% radioimpurity of 64Cu causes less than 10% deviation in activity quantitation and diminution in the therapeutic index. The change in therapeutic index is predictable over time and can be used to determine the optimal time for radiopharmaceutical administration.

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